Method for calculating filter clogging factor and bed-side system

ABSTRACT

Method for calculating a clogging factor of a filter composed of hollow-fiber membrane, which has a blood inflow portion  32   a  and a blood outflow portion  32   b , by passing a blood, the method including the steps of measuring at least two pressure selected from the group consisting of a pressure (Pa) in said blood inflow portion, a pressure (Pv) in said blood outflow portion, a filtering pressure (Pf 1 ) in said blood inflow portion, and a filtering pressure (Pf 2 ) in said blood outflow portion and calculating a filter clogging factor in vertical direction and/or a filter clogging factor in lateral direction using at least two of the measured pressures, flow rate information, biometric information (viscosity information and so on), and structure information.

BACKGROUOND OF THE INVENTION

1. Field of the Invention

The present invention relates to a method for calculating filterclogging factor, method and apparatus for monitoring filter clogging,and bed-side system provided with an apparatus for monitoring a filterclogging factor, which are used in the blood purification method.

2. Description of Related Art

A blood purification method can be roughly classified into two types.One is a type that removes substances in the blood through removal toliquid waste (dialysis, filtering) or adsorption into membranes when theblood flows in hollow-fibers of a filter, and hemodialysis,hemofiltering, hemodiafiltering, plasma exchange, double filteringplasmapheresis, plasmapheresis are some examples of this type. The otheris a type that removes substances in the blood through adsorption intoan adsorbent in a filter when the blood passes through the adsorbent(cloth, bead, etc.), and blood adsorption is an example of this type.

A blood purification method requires a filter for filtering blood. Whenthe purification method is actually applied, several tens of types offilters with different membrane materials, membrane areas and shapes areused at clinical work front depending on the type of the bloodpurification method applied, clinical conditions of the patient, etc.For example, when a filter with a large membrane area is used, thecapacity of removal of substances may be improved, but the amount ofblood retained outside the body (in the filter) increases, whichincreases the possibility of causing a blood pressure drop, andtherefore it is essential to select a filter suited to the physicalconstitution and clinical conditions of the patient. Furthermore, bloodpurification apparatuses and blood purification circuits of differenttypes (manufacturing companies, model numbers) are used.

Since clogging of filter in this blood purification method may causeproblems in terms of safety and economical efficiency, anti-cloggingmeasures by using an anticoagulant or adjusting flow rate, etc., aretaken on the medical work front.

Overdosage of this anticoagulant in an attempt to prevent clogging of afilter may not only cause a danger of producing serious hemorrhagiccomplications (cerebral hemorrhage, etc.) but also raise an economicalquestion because the anticoagulant is expensive. Therefore, it isdesirable to discover clogging of a filter in an early stage, adjust theamount of dosage of the anticoagulant appropriately and adjust its flowrate to prevent the progress of clogging. However, it is difficult thata level of filter clogging is monitored accurately.

Filter clogging is currently monitored only based on pressure indicesand the degree of clogging is experimentally presumed by observingvariations in the pressure indices. However, in the case of monitoringonly based on pressure indices, if any one of the types of the filter,blood purification apparatus and blood purification circuit used changesor the flow rate setting changes in the execution of the bloodpurification method or further the viscosities of the blood and liquidwaste change, then the measured pressure changes though the degree offilter clogging remains the same. Therefore, it has been impossible toprecisely evaluate a filter clogging situation or make a comparativeanalysis of the blood purification method adopted under variousconditions (using various filters, blood purification apparatuses, bloodpurification circuits, flow rate settings, viscosities of blood andliquid waste, etc.) based on pressure indices alone.

Furthermore, in a hemodialysis or hemodiafiltering, etc., it is knownthat mixing of substances contained in a dialyzing fluid with the bloodor so-called back-filtration may take place near the blood outflowportion of the filter. This back-filtration has the function ofpreventing filter clogging. However, if filtering pressure measured atone point is used, it is difficult that filter clogging in filter havingback-filtration is monitored accurately.

SUMMARY OF THE INVENTION

The present invention has been implemented in view of theabove-described problems, and it is an object of the present inventionto provide a method for calculating a filter clogging factor, method andapparatus for monitoring filter clogging on the basis of the filterclogging factor, and a blood purification apparatus provided with theapparatus for monitoring the filter clogging factor in order toprecisely and specifically monitoring filter clogging in bloodpurification for patients having various conditions of a disease usingdifferent filters, blood purification apparatus, or blood purificationcircuits in several flow rate settings (including back-filtration).

The present invention provides a method for calculating a cloggingfactor of a filter composed of hollow-fiber membrane, which has a bloodinflow portion and a blood outflow portion, for filtering a blood bypassing said blood, said method comprising the steps of: measuring atleast two pressure selected from the group consisting of a pressure insaid blood inflow portion, a pressure in said blood outflow portion, afiltering pressure in said blood inflow portion, and a filteringpressure in said blood outflow portion; and calculating a filterclogging factor indicating the reduction in flowing ease of the blood insaid filter and/or a filter clogging factor indicating the reduction inease of filtering of said filter, by using the measured pressure.

It is also possible to integrate at least two of the flow rateinformation, measured pressure indices, biometric information (viscosityinformation) and/or filter structure information, and further obtain acorrection coefficient calculated from the pressure indices duringpriming (operation to connect a circuit and clean the circuit withphysiological saline: preparation stage prior to clinical use or afterstarting blood purification process) and thereby monitor the clogging ofa filter irrespective of factors affecting the pressure indices (filterstructure, blood purification apparatus, blood purification circuit,flow rate, biometric factor).

According to this method, it is possible to discover filter clogging inan early stage, appropriately adjust the amount of dosage of ananticoagulant without overdosage, change a flow rate setting and therebyprevent the progress of filter clogging. Furthermore, it is alsopossible to set a flow rate considering back-filtration of each filterby controlling back-filtration.

In the method for calculating a clogging factor of a filter according tothe present invention, it is preferable to calculate a filter cloggingfactor indicating the reduction in flowing ease of the blood in thefilter by using a viscosity of blood. This makes it possible toprecisely evaluate a level of clogging indicating the reduction inflowing ease of the blood in the filter.

In the method for calculating a clogging factor of a filter according tothe present invention, a filter clogging factor indicating the reductionin flowing ease of the blood in said filter is calculated by usingstructure information and/or flow rate information of the filter. Thismakes it possible to precisely evaluate a level of clogging indicatingthe reduction in flowing ease of the blood in the filter.

In the method for calculating a clogging factor of a filter according tothe present invention, it is preferable to calculate a filter cloggingfactor [F(%)], which the reduction in flowing ease of the blood in saidfilter is represented by the decreasing rate in a cross sectional areainside said hollow-fiber, by using the Equation (1):F=100{1−[10⁻⁹ ·K·l·η _(b)·(Q _(b) −Q _(f)/2)/N/ΔP _(b)′/π]^(0.5) /R ₀²}  Equation (1)where K represents a correction coefficient (−), η_(b) representsviscosity (Pa·sec) of the blood, Q_(b) represents flow rate (ml/min) ofthe blood flowing into the filter, Q_(f) represents filtering flow rate(ml/min), N represents the number of hollow-fibers (−), ΔP_(b)′represents a difference (mmHg) of the pressure between both ends of thehollow-fiber, l represents an effective length (m) of the hollow-fiber,and R₀ represents the radius (m) inside the hollow-fiber that theclogging does not occur.

In the method for calculating a clogging factor of a filter according tothe present invention, it is preferable to calculate a filter cloggingfactor [F(%)], which the reduction in flowing ease of the blood in saidfilter is represented by the decreasing rate in a cross sectional areainside said hollow-fiber, by using the Equation (2):F=100{1−[K′·← _(b)(Q _(b) −Q _(f)/2)/ΔP _(b)′]^(0.5)}  Equation (2)where K′ represents a correction coefficient (−), η_(b) representsviscosity (Pa·sec) of the blood, Q_(b) represents flow rate (ml/min) ofthe blood flowing into the filter, Q_(f) represents filtering flow rate(ml/min), and A P_(b)′ represents a difference (mmHg) of the pressurebetween both ends of the hollow-fiber.

In the method for calculating a clogging factor of a filter according tothe present invention, it is preferable to calculate a filter cloggingfactor indicating the reduction in flowing ease of the blood in saidfilter in real-time.

In the method for calculating a clogging factor of a filter according tothe present invention, it is preferable to calculate a filter cloggingfactor indicating the reduction in ease of filtering using the filter byusing a viscosity of liquid waste.

In the method for calculating a clogging factor of a filter according tothe present invention, a filter clogging factor indicating the reductionin ease of filtering of the filter is calculated by using structureinformation and/or flow rate information of the filter. This makes itpossible to precisely evaluate a level of clogging indicating thereduction in ease of filtering of the filter.

In the method for calculating a clogging factor of a filter according tothe present invention, it is preferable to calculate a filter cloggingfactor [f(%)], which the reduction in ease of filtering of said filteris represented by the decreasing rate in a cross sectional area of poreof said hollow-fiber, by using the Equation (3):f=100[1−(10⁻⁹ ·k·τ·ΔX·η _(w) ·Q _(f) /r ₀ ² /A _(k) /A _(m) /ΔP_(w)′)^(0.5)]  Equation (3)where k represents a correction coefficient (−), τ represents a rate ofcurved path, Δ X represents a thickness of a membrane, η_(w) representsa viscosity of liquid waste passing a filter (Pa·sec), Q_(f) representsfiltering rate (ml/min), r₀ represents the radius (m) of a hollow-fibermembrane pore that the clogging does not occur, ΔP_(w)′ represents adifference of the pressure between the blood side end and the liquidwaste side end in the membrane pore of the filter (mmHg), A_(k)represents a proportion of a cross sectional area of the membrane poreto a unit area of the membrane in the filter, and A_(m) represents anarea (m²) of the membrane in the filter.

In the method for calculating a clogging factor of a filter according tothe present invention, it is preferable to calculate a filter cloggingfactor [f(%)], which the reduction in ease of filtering of said filteris represented by the decreasing rate in a cross sectional area of poreof said hollow-fiber, by using the Equation (4):f=100[1−(k′·η _(w) ·Q _(f) /ΔP _(w)′)^(0.5)]  Equation (4)where k′ represents a correction coefficient (−), η_(w) represents aviscosity of liquid waste passing a filter (Pa·sec), Q_(f) representsfiltering rate (ml/min), r represents the radius (m) of a hollow-fibermembrane pore that the clogging does not occur, and ΔP_(w)′ represents adifference of the pressure between the blood side end and the liquidwaste side end in the membrane pore of the filter (mmHg).

In the method for calculating a clogging factor of a filter according tothe present invention, it is preferable to calculate a filter cloggingfactor indicating the reduction in ease of filtering of the filter inreal-time.

In the method for calculating a clogging factor of a filter according tothe present invention, it is preferable to calculate a filter cloggingfactor [S(−)], which the reduction in flowing ease of the blood in thefilter is represented by the decreasing rate in a cross sectional areainside said hollow-fiber, by using the Equation (5):S=[η _(b)·(Q _(b) −Q _(f)/2)·ΔP _(b0)′/η_(b0)/(Q _(b0) −Q _(f0)/2)/ΔP_(b)′]^(0.5)  Equation (5)wherein η_(b) represents viscosity (Pa·sec) of the blood flowing in thehollow-fiber, η_(b0) represents viscosity (Pa·sec) of the priming liquidin the priming, Q_(b) represents flow rate (ml/min) of the blood flowinginto the filter, Q_(b0) represents flow rate (ml/min) of the primingliquid flowing into the filter in the priming, Q_(f) representsfiltering flow rate (ml/min), Q_(f0) represents filtering flow rate(ml/min) of the priming liquid flowing into the filter, ΔP_(b)′represents a difference (mmHg) (Pa−Pv) of the pressure between both endsof the hollow-fiber, and ΔP_(b0)′ represents a difference (mmHg) of thepressure between both ends of the hollow-fiber in the priming. Here,values (viscosity of the blood flowing in the hollow-fiber, flow rate ofthe blood flowing into the filter, filtering flow rate, a difference ofthe pressure between both ends of the hollow-fiber), that are obtainedafter starting blood purification process, may be used as η_(b0),Q_(b0), Q_(f0) and ΔP_(b0)′.

In the method for calculating a clogging factor of a filter according tothe present invention, it is preferable to calculate a filter cloggingfactor [s(−)], which the reduction in ease of filtering of the filter isrepresented by the decreasing rate in a cross sectional area of membranepore of said hollow-fiber, by using the Equation (6):S=(η_(w) ·Q _(f) ·ΔP _(w0) ′/η _(w0) /Q _(f0) /ΔP _(w)′)^(0.5)  Equation(6)wherein η_(w) represents viscosity (Pa·sec) of the liquid waste, ηw₀represents viscosity (Pa·sec) of the liquid waste in the priming, Q_(f)represents filtering flow rate (ml/min), Q_(f0) represents filteringflow rate (ml/min) of the priming liquid, ΔP_(w)′ represents adifference (mmHg) of the pressure between blood side end and liquidwaste side end of the hollow-fiber membrane pore, ΔP_(w0)′ represents adifference (mmHg) of the pressure between blood side end and liquidwaste side end of the hollow-fiber membrane pore in the priming, and srepresents a ratio of cross sectional areas in the hollow-fiber membranepore of the filter. Here, values (viscosity of the liquid waste,filtering flow rate, a difference of the pressure between blood side endand liquid waste side end of the hollow-fiber membrane pore), that areobtained after starting blood purification process, may be used asη_(w0), Q_(f0) and ΔP_(w0)′.

This makes it possible to eliminate the influences of errors included inthe correction coefficient in the calculation equation of the filterclogging factor and monitor the filter clogging more preciselyirrespective of factors affecting the pressure indices (filterstructure, blood purification apparatus, blood purification circuit,flow rate, biometric factor).

In the method for calculating a clogging factor of a filter according tothe present invention, it is preferable to use an average of ΔPW′ in theblood inflow portion and ΔPW′ in the blood outflow portion of the filteras A PW′.

The present invention provides a method for monitoring a clogging of afilter comprising the steps of calculating a clogging factor of a filterby using the above-described method for calculating a clogging factor ofa filter and monitoring a clogging of a filter on the basis of theclogging factor of a filter.

Furthermore, the present invention provides an apparatus for monitoringa clogging of a filter comprising means for calculating a cloggingfactor of a filter by using the above-described method for calculating aclogging factor of a filter and means for monitoring a clogging of afilter on the basis of the clogging factor of a filter.

Furthermore, the present invention provides a bed-side system comprisingthe above-described apparatus for monitoring a clogging of a filter.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 a is a view showing a filter used in the blood purification;

FIG. 1 b is a view showing a hollow-fiber in a filter;

FIG. 2 is a view to explain a clogging in vertical direction and inlateral direction;

FIG. 3 is a view to explain a portion of measuring the pressure that isused in a method according to the present invention;

FIG. 4 is a view to explain the pressure that is used in a methodaccording to the present invention;

FIG. 5 is a view to explain the back-filtration;

FIG. 6 is a view showing an arrangement of a bed-side system whichimplements a method according to the present invention;

FIG. 7 illustrates a variation of the clogging factor (F) in thevertical direction when sustained blood filtering was performed;

FIG. 8 illustrates a variation of the clogging factor (f) in thehorizontal direction when sustained blood filtering was performed;

FIG. 9 illustrates a variation of a pressure index Pa−Pv and a variationof the clogging factor (F) in the vertical direction caused by avariation in the blood flow rate;

FIG. 10 shows a simulation curve indicating a relationship between thepressure index Pa−Pv and clogging factor F (%) in the verticaldirection; and

FIG. 11 illustrates a variation of the clogging factor (s) in thehorizontal direction when sustained blood filtering was performed.

DESCRIPTION OF THE PREFERRED EMBODIMENT(S)

The present inventors have noticed the fact that there are two modes offilter clogging; (vertical) clogging indicating the reduction in flowingease of the blood in the filter and (lateral) clogging indicating thereduction in ease of filtering using the filter, and have come up withthe present invention by discovering that it is possible to accuratelymonitor filter clogging by calculating a filter clogging factor on thebasis of a relationship between clogging in each mode of clogging andpressure.

That is, a subject matter of the present invention is to measure atleast two pressures selected from the group consisting of a pressure inthe blood inflow portion, a pressure in the blood outflow portion, afiltering pressure in the blood inflow portion, and a filtering pressurein the blood outflow portion of the filter and calculate filter cloggingfactors in vertical direction and lateral direction using the measuredpressures. This makes it possible to discover filter clogging in anearly stage, appropriately adjust the amount of dosage of ananticoagulant without overdosage, change a setting of flow rate of bloodand thereby prevent the progress of filter clogging.

Furthermore, it is also possible to integrate at least two the flow rateinformation, measured pressure indices, biometric information (viscosityinformation and so on) and/or filter structure information, and furtherobtain a correction coefficient calculated from the pressure indicesduring priming (operation to connect a circuit and clean the circuitwith physiological saline: preparation stage prior to clinical use) andthereby monitor the clogging of a filter irrespective of factorsaffecting the pressure indices (filter structure, blood purificationapparatus, blood purification circuit, flow rate, biometric factor).

With reference now to the attached drawings, embodiments of the presentinvention will be explained in detail below.

First, a filter clogging mode will be explained using FIG. 1. A filter 1used for blood purification is composed of on the order of severalthousand to 10,000 hollow-fibers 11 placed in a housing 10 as shown inFIG. 1(a), each hollow-fiber 11 having an effective length ofapproximately 150 to 250 mm and an inside diameter of approximately 200μm in a humid condition. This filter 1 is connected to a circulationpath 2 for circulating bodily fluids such as blood. Furthermore as shownin FIG. 1(b), many membrane pores 12 of several hundred nanometers indiameter are formed on the side of the hollow-fibers 11. Clogging insuch hollow-fibers during blood purification of the hollow-fibers can beroughly classified into two types of clogging; clogging inside of thehollow-fibers (clogging indicating the reduction in flowing ease of theblood: vertical clogging) and clogging of membrane pores of thehollow-fiber membranes (clogging indicating the reduction in ease offiltering: lateral clogging).

Clogging in the hollow-fibers during blood purification process may becaused by 1) adsorption of protein onto the membrane surface or into themembrane, 2) adhesion or invagination of fibrin onto the membranesurface, 3) adhesion or invagination of blood platelets onto themembrane surface, 4) adhesion of white blood cells onto the membranesurface, 5) adhesion of red blood cells onto the membrane surface, and6) adhesion of medicine onto the membrane surface or into the membrane,etc.

As shown in FIG. 2, adhesion of substances onto the membrane surface ofthe hollow-fibers causes not only clogging (lateral clogging) A ofmembrane pores 112 of the hollow-fiber membrane 111 of the hollow-fiber11 but also clogging inside of the hollow-fiber 113 (vertical clogging)B due to a narrowing of the inside 113 of the hollow-fibersimultaneously. The clogging inside 113 of the hollow-fiber (verticalclogging) B is only caused by adhesion of substances (e.g., protein,fibrin, blood platelets, blood cells, medicine) 114 onto the surface ofthe hollow-fiber membrane 111, while clogging (lateral clogging) A ofmembrane pores 112 of the hollow-fiber membrane 111 is caused byadhesion of the substances 114 not only onto the surface of thehollow-fiber membranes 111 but also into the membrane pores 112 of thehollow-fiber membrane 111. Furthermore, liquid waste (filtrate,dialyzing fluid) exists outside the hollow-fibers.

Clogging inside the hollow-fiber (vertical clogging) B causes thereduction in the blood flow rate in the hollow-fiber where the cloggingoccurs and the reduction in the ability to remove substances by means ofdiffusion. The reduction in the blood flow rate facilitates adhesion ofsubstances onto the membrane and makes clogging more likely to occur.Complete clogging of the inside of the hollow-fibers not only makes itimpossible to remove substances of the hollow-fibers at the outlet fromthe clogged portion but also allows to the blood to remain in the filter(residual blood) at the end of blood purification, leading to a bloodloss of the patient.

Clogging (lateral clogging) A of membrane pores of the hollow-fibermembrane involves a danger of causing the reduction in the ability toremove substances (clearance), suctions blood cells that have a largerdiameter than membrane pores and do not pass through the membrane poresby a strong negative pressure and has a possibility of causingdestruction of blood cells (hemolysis, etc.). The ease of filteringrefers to ease of filtrate that passes through the filter with which thefiltrate passes to the liquid waste side, and this reduces when theclogging factor f of a filter increases and when the clogging factor sof a filter decrease.

Portions of clogging of these membranes and the degree of clogging aredetermined by 1) conditions for executing blood purification processsuch as type of a filter, flow rate setting, type and amount of dosageof a coagulant, type of substitution liquid and dialyzing fluid, 2)clinical condition of the patient, 3) medical treatment conditions suchas blood transfusion, medicine, medical treatment, etc. Here, adhesionof substances onto the surface of the hollow-fiber membrane is relatedto clogging in vertical direction and clogging in lateral direction,while adhesion of substances into membrane pores of the hollow-fibermembrane is related to clogging in lateral direction.

As a method for detecting a level of clogging of a filter, there is amethod whereby a pressure in a filter and/or a blood purificationcircuit is measured and a clogging factor of the filter is calculated onthe basis of information on the pressure. This embodiment uses apressure measured in a drip-chamber in the blood inflow portion locatedbetween a blood roller pump and the filter (blood inflow portionpressure (arterial pressure: Pa)), a pressure measured in a drip-chamberin the blood outflow portion located after the filter (blood outflowportion pressure (venous pressure: Pv)), a pressure measured outside thehollow-fiber on the blood inflow portion side of the filter (filteringpressure in the blood inflow portion: Pf1) and a pressure measuredoutside the hollow-fiber on the blood outflow portion side of the filter(filtering pressure in the blood outflow portion: Pf2) and calculatesfilter clogging factors in vertical direction and in lateral directionusing other information ((flow rate information, biometric information(viscosity information and the like), filter structure information(membrane material, diameter of hollow-fiber, effective length ofhollow-fiber, membrane area, membrane thickness, rate of hollow area,rate of curved path, diameter of membrane pore)).

As will be described later, the filter clogging factor according to thepresent invention is calculated based on the Hagen-Poiseuille law.However, filter structure information substituted into theHagen-Poiseuille law for calculating the filter clogging factor is ageneral value. There is a difference between the general value and avalue used actually. Further, it is necessary to calculate a filterclogging factor with correcting errors during pressure measurement(pressure loss of blood purification circuit) or errors of biometricinformation (values calculated by an approximate expression).

Thus, in the present invention, for evaluating a level of filterclogging more accurately, a filter clogging factor (F, f) is calculatedby equations including correction coefficients K, K, k and k′, and afilter clogging factor (S, s) is calculated.

When a clogging factor in vertical direction is calculated, the cloggingfactor is calculated using at least two of a correction coefficient, aflow rate of the blood, pressure information (a difference of thepressure between the blood inflow portion pressure and the blood outflowportion pressure and so on), biometric information (viscosityinformation), and filter structure information (the number ofhollow-fibers, radius of the hollow-fiber that the clogging does notoccur, and so on). In this case, the blood viscosity can be calculatedusing any one of the following methods:

-   1. Approximation using hematoclit value continuously measured by a    clitline monitor or actually measured hematoclit value (Ht) and    actually measured blood protein level (TP).-   2. Approximation using only hematoclit value continuously measured    by a clit line monitor or actually measured hematoclit value (Ht).-   3. Actual measurement by viscometer

The difference of the pressure Pa−Pv can be calculated continuously fromthe actually measured values of Pa and Pv and the flow rate of the bloodis a set value, and therefore by approximating a blood viscosity usinghematoclit value continuously measured by a clitline monitor or onlyactually measured hematoclit value, it is possible to calculate a filterclogging factor in vertical direction in real-time.

When a clogging factor in lateral direction is calculated, the cloggingfactor is calculated using at least two of a correction coefficient, aflow rate of filtering, pressure information (TMP (transmembranepressure), which is a difference of the pressure between membranesrepresenting a pressure that contributes to filtering, biometricinformation (viscosity of liquid waste and so on) and filter structureinformation (radius of the hollow-fiber that the clogging does notoccur, rate of curved path, membrane thickness and so on). In this case,the viscosity of liquid waste can be obtained by an actual measurement.The TMP can be calculated using any one of the following methods:

-   1. Calculation by obtaining blood inflow portion pressure Pa, blood    outflow portion pressure Pv, filtering pressure at the blood inflow    portion Pf1 and filtering pressure at the blood outflow portion Pf2    continuously through actual measurements and using the actually    measured values.-   2. Calculation using the actually measured values of Pa, Pv, Pf1 and    Pf2, blood colloidal osmotic pressure actually measured using a    colloidal osmotic pressure gauge and Staverman's coefficient of    restitution.-   3. Calculation using the actually measured values of Pa, Pv, Pf1 and    Pf2, blood colloidal osmotic pressure approximated by Alb/Glb    obtained through a clinical examination and Staverman's coefficient    of restitution.-   4. Calculation using the actually measured values of Pa, Pv, Pf1 and    Pf2, blood colloidal osmotic pressure actually measured using a    colloidal osmotic pressure gauge and colloidal osmotic pressure of    liquid waste.

Thus, by combining pressure information and colloidal osmotic pressureinformation, it is possible to grasp back-filtration of hemodialysis andgrasp clogging in lateral direction more precisely.

Then, portions of measuring Pa, Pv, Pf1 and Pf2 will be explained. Pa,Pv, Pf1 and Pf2 will be measured at the portions shown in FIG. 3. InFIG. 3, a roller pump 31 is connected to a circulation path 30 alongwhich the blood flows. This roller pump 31 circulates blood (bodilyfluid) through the circulation path 30 outside the body. The circulationpath 30 is provided with a filter 32 that filters the blood. This filter32 is provided with a blood inflow portion 32 a and blood outflowportion 32 b, also provided with a coupler 32 c of the blood inflowportion and a coupler 32 d of the blood outflow portion which serve asthe outlet and inlet of a dialyzing liquid and liquid waste. Thecouplers 32 c and 32 d are connected to their respective tubes (notshown) and the pressures in those tubes become the filtering pressure ofthe blood inflow portion (Pf1) and the filtering pressure of the bloodoutflow portion (Pf2) respectively.

Furthermore, before the filter 32 on the circulation path 30, a bloodinflow portion drip-chamber 33 is provided. On the other hand, after thefilter 32 on the circulation path 30, a blood outflow portiondrip-chamber 34 is provided. According to this embodiment, the pressuresPa and Pv of the blood inflow portion 32 a and blood outflow portion 32b of the filter 32 are measured at the blood inflow portion drip-chamber33 and blood outflow portion drip-chamber 34. However, if the pressuresin the blood inflow portion 32 a and blood outflow portion 32 b of thefilter 32 can be measured, the Pa and Pv can also be measured at anyportions other than the blood inflow portion drip-chamber 33 and bloodoutflow portion drip-chamber 34.

In such a configuration, a blood inflow portion pressure (arterialpressure: Pa) is measured at the blood inflow portion drip-chamber 33and a blood outflow portion pressure (venous pressure: Pv) is measuredat the blood outflow portion drip-chamber 34, a filtering pressure (Pf1)of the blood inflow portion is measured at the tube connected to thecoupler 32 c of the blood inflow portion and a filtering pressure (Pf2)of the blood outflow portion is measured at the tube connected to thecoupler 32 d of the blood outflow portion. By the way, the methods formeasuring pressures at the respective portions are the same as themethod for measuring pressures during normal detection of filterclogging.

Then, a filter clogging factor will be calculated using at least two ofthe pressure information, flow rate information, biometric information(viscosity information, osmotic pressure information and so on) andstructure information measured as described above. The hematoclit valuethat defines a blood viscosity can be collected continuously using acontinuous hematoclit monitor. The continuous hematoclit monitor isdescribed in the Japanese Patent Application No. 2000-397609, thecontent of which is also included herein. Thus, calculating a filterclogging factor by combining at least two of the pressure information,flow rate information (blood flow, filtering), biometric information(viscosity information, osmotic pressure information and so on) andfilter structure information will make it possible to grasp cloggingmore precisely.

(Calculation of Filter Clogging Factor [F(%)] in Vertical Direction)

A difference Pa−Pv (a in FIG. 4) of the pressure between the bloodinflow portion pressure (arterial pressure: Pa) and blood outflowpressure (venous pressure: Pv) is one of factors expressing clogging(clogging in vertical direction) of the hollow-fiber of a filter.According to a labyrinthine membrane pore theory, which is well known inthe art, when a fluid flows in a laminar flow in the hollow-fibers of afilter, Pa, Pv is defined by blood flow rate Q_(b) and blood viscosityη_(b) according to Hagen-Poiseuille law. Thus, it is necessary tomeasure blood viscosity η_(b) in order to evaluate clogging of thehollow-fibers of the filter (clogging in vertical direction) from Pa,Pv.

A viscosity of blood can be calculated approximately from a hematoclitvalue of the blood and/or blood protein level. A hematoclit value can bemeasured by a blood test, but when blood purification is performed, thehematoclit value changes together with water elimination and dosage of asubstitution liquid. However, when a blood purification treatment is inprogress, it is possible to collect information on a hematoclit valuenoninvasively, in real-time, continuously and automatically through acontinuous hematoclit monitor. Therefore, the information on a viscosityof blood obtained through such an approximate calculation may be used tocalculate a filter clogging factor.

According to a labyrinthine membrane pore theory, which is well known inthe art, when a fluid flows in a laminar flow in the hollow-fiber of afilter, the Hagen-Poiseuille law is held as shown in the followingequation (Equation (7)).Q=π·R ⁴ ·ΔP _(b)/8η_(b) /l  Equation (7)A=π·R ²  Equation (8)Q=(Q _(b) −Q _(f)/2)/N/(6×10⁷)  Equation (9)ΔP _(b)=133.3·ΔP _(b)′  Equation (10)where the respective parameters represent the following:

-   Q: Flow rate of blood passing through hollow-fibers (m³/sec)-   Q_(b): Flow rate of blood flowing into the filter (ml/min)-   Q_(f): Filtering flow rate (ml/min)-   R: Radius of inside of hollow-fiber (m)-   N: Number of hollow-fibers (−)-   l: Effective length of hollow-fiber (m)-   ΔP_(b): Difference of pressure between both ends of hollow-fiber    (corresponds to Pa−Pv in this case) (Pa)-   ΔP_(b)′: Difference of pressure between both ends of hollow-fiber    (corresponds to-   Pa−Pv in this case) (mmHg)-   η_(b): Viscosity of blood passing through hollow-fiber (Pa·sec)-   A: Cross sectional area of inside of hollow-fiber (m²)

From Equations (7) to (10), cross sectional area A (m²) of inside ofhollow-fiber is calculated by Equation (11):A=[10⁻⁹ ·π·l·η _(b)·(Q _(b) −Q _(f)/2)/N/ΔP_(b)′]^(0.5)  Equation (11)From Equation (11), cross sectional area A₀ (m²) of inside ofhollow-fiber in filter without clogging is calculated by Equation (12):A=[10⁻⁹ ·π·l ·η _(b0)·(Q _(b0) −Q _(f0)/2)/N/ΔP _(b0)′]^(0.5)  Equation(12)where the respective parameters represent the following:

-   η_(b0): viscosity of the priming liquid (Pa·sec)-   Q_(b0): flow rate of the priming liquid flowing into the filter in    the priming (ml/min)-   Q_(f0): filtering flow rate of the priming liquid (ml/min)-   N: Number of hollow-fibers (−)-   l: Effective length of hollow-fiber (m)-   ΔP_(b0)′: a difference of the pressure between both ends of the    hollow-fiber in the priming (mmHg)-   A₀: Cross sectional area of inside of hollow-fiber without clogging    (m²)

Cross sectional area A₀ (m²) of inside of hollow-fiber in filter withoutclogging is also calculated by Equation (13):A ₀ ′=π·R ₀ ²  Equation (13)where R₀ represents radius of inside of hollow-fiber without clogging.

Although A₀ (m²) obtained by Equation (12) and A₀′ (m²) obtained byEquation (13) should be same in theory, A₀ (m²) and A₀′ (m²) are notsame in actual due to errors between general filter structureinformation and filter structure information used actually, errors inmeasuring the pressure (pressure loss of blood purification circuit andso on), and errors of biometric information (obtained by approximateequation). Therefore, it is necessary to set a correction coefficientK(−) indicating Equation (14):A ₀ ′=K ^(0.5) ·A ₀  Equation (14)A filter clogging factor F(%), which the reduction in flowing ease ofthe blood in the filter is represented by the decreasing rate in a crosssectional area inside said hollow-fiber can be calculated by Equation(15):F=100·(1−A/A ₀)  Equation (15)From Equations (14) and (15), a filter clogging factor F(%), which thereduction in flowing ease of the blood in the filter is represented bythe decreasing rate in a cross sectional area inside said hollow-fibercan be calculated by Equation (16):F=100−(1−K ^(0.5) A/A ₀′)  Equation (16)From Equations (11), (13) and (16), a filter clogging factor F(%), whichthe reduction in flowing ease of the blood in the filter is representedby the decreasing rate in a cross sectional area inside saidhollow-fiber can be calculated by Equation (1):F=100{1−[10⁻⁹ ·K·η _(b)·(Q _(b)−Q_(f)/2)/N/ΔP_(b)′/π]^(0.5) /R²}  Equation (1)From Equations (12) to (14), a correction coefficient K(−) in Equation(1) can be calculated by Equation (17):K=10⁹ ·π·R ₀ ⁴ ·N·ΔP _(b0) ′/l/η _(b0)/(Q _(b0) −Q _(f0)/2)  Equation(17)where the respective parameters represent the following:

-   Q_(b0): a flow rate of the priming liquid that flows through the    hollow-fiber in the priming (ml/min)-   Q_(f0): a filtering flow rate in the priming (ml/min)-   R₀: a radius of the hollow-fiber without clogging (m)-   N: the number of hollow-fibers (−)-   l: the effective length of the hollow-fiber (m)-   ΔP_(b0)′: a pressure difference between both ends of the    hollow-fiber in the priming (mmHg)

η_(b0): a viscosity of the priming liquid (Pa·sec).

Equation (1) includes a parameter of filter structure information (aradius of the hollow-fiber without clogging, the number of hollow-fibersand the effective length of the hollow-fiber). Thus, it is impossible tocalculate a filter clogging factor using Equation (1), if filterstructure information is not given. Therefore, if filter structureinformation is not given, a filter clogging factor F(%), which thereduction in flowing ease of the blood in the filter is represented bythe decreasing rate in a cross sectional area inside said hollow-fibercan be calculated by Equation (2) which does not include a parameter offilter structure information, by setting a correction coefficient K′(−)obtained by Equation (18):K′=10⁻⁹ ·K·l/N/ΔP _(b0) ′/π/R ₀ ⁴ Equation (18)F=100{1−[K′·η _(b0)·(Q _(b0) −Q _(f0)/2)/ΔP _(b0)]^(0.5)}  Equation (2)From Equations (17) and (18), a correction coefficient K′(−) in Equation(2) can be calculated by Equation (19):K′=ΔP _(b0)′/η_(b0)/(Q _(b0) −Q _(f0)/2)  Equation (19)where the respective parameters represent the following:

-   Q_(b0): a flow rate of the priming liquid that flows through the    hollow-fiber in the priming (ml/min)-   Q_(f0): a filtering flow rate in the priming (ml/min)-   ΔP_(b0)′: a pressure difference between both ends of the    hollow-fiber in the priming (mmHg).

Furthermore, the viscosity (η_(b)Pa·sec)) of the blood that passesthrough the hollow-fiber can be calculated approximately by using thefollowing Equation (20).lnη _(b)=10⁻² ·Ht·(−0.23TP+3.675)+(0.059TP−0.354)  Equation (20)where the symbols of the respective parameters represent the following:

-   Ht: Hematoclit value (%)-   TP: Blood protein level (g/di)

From the above Equations (1) to (20), the clogging factor F (%) of afilter in vertical direction can be calculated by using the followingEquation (1′). Here, the clogging factor F (%) of a filter in verticaldirection means a proportion of a cross sectional area of thehollow-fibers in which the blood flows to a cross sectional area insidethe hollow-fibers of a filter without clogging.F=100[1−{10⁻⁹ ·K·l·exp[10⁻² ·Ht(−0.23TP+3.675)+(0.059TP−0.354)]·(Q _(b)−Q _(f)/2)/N/ΔP _(b)′/π}^(0.5) /R ₀ ²]  Equation (1′)where K represents a correction coefficient(−) calculated by Equation(17).

From the above Equations (2) to (20), the clogging factor F (%) of afilter in vertical direction can be calculated by using the followingEquation (2′):F=100[1−{K′·exp[10⁻² ·Ht(−0.23TP+3.675)+(0.059TP−0.354)]·(Q _(b) −Q_(f)/2)/N/ΔP _(b)′/π}^(0.5)/R₀ ²]  Equation (2′)where K′ represents a correction coefficient (−) calculated by Equation(19).

Furthermore, the rate AF (%/min) of change per unit time of cloggingfactor F in vertical direction can be calculated by using the followingEquation (21):ΔF=dF/dt  Equation (21)where t represents time (min).(Calculation of Filter Clogging Factor [S(−)] in Vertical Direction)

From the above Equations (11) and (12), a filter clogging factor[S(−)](S=A/A₀) which the reduction in flowing ease of the blood in thefilter is represented by a ratio of a cross sectional area inside thehollow-fiber, is obtained by Equation (5).S=[η _(b)·(Q _(b)−Q_(f)/2)ΔP_(b0)′/η_(b0)/(Q _(b0) −Q_(f0)/2)/ΔP_(b)′]^(0.5)  Equation (5)where the respective parameters represent the following:

-   ηb: viscosity of the blood flowing in the hollow-fiber (Pa·sec)-   ηb₀: viscosity of the priming liquid in the priming (Pa·sec)-   Q_(b): flow rate of the blood flowing into the filter (ml/min)-   Q_(b0): flow rate of the priming liquid flowing into the filter in    the priming (ml/min)-   Q_(f): filtering flow rate (m/min)-   Q_(f0): filtering flow rate in the priming (ml/min)-   ΔP_(b)′: a difference of the pressure between both ends of the    hollow-fiber (mmHg) (Pa−Pv)-   ΔP_(b0)′: a difference of the pressure between both ends of the    hollow-fiber in the priming (mmHg).

Thus, calculated is a filter clogging factor [S(−)](S=A/A₀) which thereduction in flowing ease of the blood in the filter is represented by aratio of a cross sectional area inside the hollow-fiber using flow rateinformation, measured pressure indices and biometric information(viscosity information). This makes it possible to eliminate theinfluences of errors included in the correction coefficient (K,K′) inthe calculation equation of the filter clogging factor and monitor thefilter clogging more precisely irrespective of factors affecting thepressure indices (filter structure, blood purification apparatus, bloodpurification circuit, flow rate, biometric factor).

In this embodiment, parameters R₀, N and 1 are defined by the type ofthe filter and the respective parameters are collected as follows:

-   R₀, N, l: Manually input-   Q_(b): Measured by the blood purification apparatus and    automatically input continuously in real-time.-   ΔP_(b)′ (=Pa−Pv): Measured by the blood purification apparatus or    pressure information collection apparatus and automatically input    continuously in real-time.-   Ht: Measured by the continuous hematoclit monitor and automatically    input continuously in real-time.-   TP: Blood protein level (g/dl) (measured several times a day by a    blood test and values are manually input)

However, the input method is not limited to the above-described method.

(Calculation of Filter Clogging Factor [f(%)] in Lateral Direction)

According to a labyrinthine membrane pore theory, which is well known inthe art, when a fluid flows in a laminar flow through membrane pores inthe hollow-fibers of a filter, the Hagen-Poiseuille law is held as shownin the following equation (Equation (22)):Q=π·r ⁴ ·ΔP _(w)/8η_(w) /l  Equation (22)A=τr ²  Equation (23)l=τ·ΔX  Equation (24)Q=Q _(f)/(6×10⁷ ·A _(k) ·A _(m) ·τr ²)  Equation (25)ΔP _(w)=133.3·ΔP _(w)′  Equation (26)where the respective parameters represent the following:

-   Q: Flow rate of blood passing through membrane pore (m³/min)-   Q_(f): Filtering rate (ml/min)-   r: Radius of hollow-fiber (m)-   l: Effective length of hollow-fiber (m)-   τ: Rate of curved path (m)-   ΔX: Thickness of membrane (m)-   ΔP_(w): Difference of pressure between blood side end and liquid    waste side end of membrane pore of filter (mmHg)-   ΔP_(w)′: Difference of pressure between blood side end and liquid    waste side end of membrane pore of filter (mmHg)-   η_(w): Viscosity of blood passing through membrane pore (Pa sec)-   A: Cross sectional area of membrane pore of hollow-fiber (m²)-   A₀: Cross sectional area of membrane pore of hollow-fiber that the    clogging does not occur (m²)-   A_(k): Proportion of cross sectional area of membrane pore to unit    area of membrane (−)-   A_(m): Area of membrane (m²).

ΔP_(w)′ is also a pressure actually contributing to filtering at thecenter of the filter (effective filtering pressure) and a TMP(transmembrane pressure) calculated by Equation (27) that takes intoaccount an osmotic pressure (σΔΠ) by membrane impermeable substancesthat exist on the blood side. TMP is a difference of the pressurebetween membranes indicating a pressure that contributes to filtering.This TMP increases as clogging of a filter advances, and therefore TMPnot only represents a pressure that contributes to filtering but is alsoused as a factor for evaluating clogging of a filter.TMP=(Pa+Pv)/2−(Pf 1+Pf 2)/2−σΔΠ  Equation (27)

-   AΠ: Colloidal osmotic pressure by protein (mmHg)-   σ: Staverman's coefficient of restitution (proportion of solute that    cannot permeate membrane)(−)

From Equations (22) to (26), cross sectional area a (m²) of membranepore is calculated by Equation (28):a=[10⁻⁹π²·r²τ·ΔX·η_(w)·Q_(f) /A _(k)/A_(m)/ΔP_(w)′,]^(0.5)  Equation(28)From Equation (28), cross sectional area a₀ (m²) of membrane porewithout clogging is calculated by Equation (29):a ₀=[10⁻⁹ ·π ² r ₀ ² τ·ΔX·η _(w0) ·Q_(f0)/A_(k)/A_(m)ΔP_(w0)′]^(0.5)  Equation (29)where the respective parameters represent the following:

-   Q_(f0): filtering flow rate in the priming (ml/min)-   r₀: the radius of the hollow-fiber without clogging (m)-   τ: a rate of curved path (−)-   ΔX: membrane thickness (m)-   ΔP_(w0)′: a difference of the pressure between blood side end and    liquid waste side end of the hollow-fiber membrane pore in the    priming (mmHg)-   η_(w0): the viscosity of the priming liquid (Pa−sec)-   a₀: cross sectional area of membrane pore without clogging (m²)-   A_(k): the ratio of the cross sectional area of a membrane pore to a    unit area (−)-   A_(m): membrane area (m²)

Cross sectional area a₀ (m²) of inside of hollow-fiber in filter withoutclogging is also calculated by Equation (30):a ₀ ′=πr ₀ ²  Equation (30)where r₀ represents radius of membrane pore without clogging.

Although a₀ (m²) obtained by Equation (29) and a₀′(m²) obtained byEquation (30) should be same in theory, a₀ (m²) and a₀′ (m²) are notsame in actual due to errors between general filter structureinformation and filter structure information used actually and errors inmeasuring the pressure (pressure loss of blood purification circuit andso on). Therefore, it is necessary to set a correction coefficient k(−)indicating Equation (31):a ₀ ′=k ^(0.5)·a₀  Equation (31)

A filter clogging factor f(%), which the reduction in ease of filteringof the filter is represented by the decreasing rate in a cross sectionalarea of membrane pore can be calculated by Equation (32):f=100·(1−a/a ₀)  Equation (32)

From Equations (31) and (32), a filter clogging factor F(%), which thereduction in ease of filtering of the filter is represented by thedecreasing rate in a cross sectional area of membrane pore can becalculated by Equation (33):f=100·(1−k ^(0.5) ·a/a ₀ ′)  Equation (33)

From Equations (28), (30) and (33), a filter clogging factor f(%), whichthe reduction in ease of filtering of the filter is represented by thedecreasing rate in a cross sectional area of membrane pore can becalculated by Equation (3):f=100{1−[10⁻⁹ ·k·τΔX·η _(w) ·Q _(f) /r ₀ ² /A _(k) /A _(m) /ΔP_(w)′]^(0.5)}  Equation (3)

From Equations (29) to (31), a correction coefficient k(−) in Equation(3) can be calculated by Equation (34):k=10⁹ ·r ₀ ² ·A _(k) ·A _(m) ΔP _(w0) ′/τ/ΔX/η _(w0) /Q _(f0)  Equation(34)where the respective parameters represent the following:

-   Q_(f0): the filtering flow rate in the priming (ml/min)-   r₀: the radius of the hollow-fiber without clogging (m)-   τ: a rate of curved path (−)-   ΔX: membrane thickness (m)-   ΔP_(w0)′: a pressure difference between the blood side end and the    liquid waste side of the hollow-fiber membrane pore in the priming    (mmHg)-   η_(w0): the viscosity of the priming liquid (Pa·sec)-   a₀: cross sectional area of membrane pore without clogging (m²)-   A_(k): the ratio of the cross sectional area of a membrane pore to a    unit area (−)-   A_(m): membrane area (m²)

Equation (3) includes a parameter of filter structure information (aradius of membrane pore of hollow-fiber without clogging, the ratio ofthe cross sectional area of a membrane pore to a unit area and membranearea). Thus, it is impossible to calculate a filter clogging factorusing Equation (3), if filter structure information is not given.Therefore, if filter structure information is not given, a filterclogging factor f(%), which the reduction in ease of filtering of thefilter is represented by the decreasing rate in a cross sectional areaof membrane pore can be calculated by Equation (4) which does notinclude a parameter of filter structure information, by setting acorrection coefficient k′(−) obtained by Equation (35):k′=10⁻⁹·k·τ·ΔX/r₀ ² /A _(k) /A _(m)  Equation (35)f=100[1−(k′-η _(w) ·Q _(f) /ΔP _(w)′)^(0.5)]  Equation (4)

From Equations (34) and (35), a correction coefficient k′(−) in Equation(4) can be calculated by Equation (36):k′=ΔP _(w0)′/η_(w0) /Q _(f0)  Equation (36)where the respective parameters represent the following:

-   Q_(b0): a flow rate of the priming liquid that flows through the    hollow-fiber in the priming (ml/min)-   Q_(f0): a filtering flow rate in the priming (ml/min)-   ΔP_(b0)′: a pressure difference between both ends of the    hollow-fiber in the priming (mmHg).

Furthermore, the rate of change per unit time of clogging factor f inlateral direction Δf (%/min) can be calculated by using the followingEquation (37).Δf=df/dt  Equation (37)where t represents time (min).(Calculation of Filter Clogging Factor [s(−)] in Lateral Direction)

From the above Equations (28) and (29), obtained is a filter cloggingfactor s(−) which the reduction in ease of filtering of the filter isrepresented by a ratio of a cross sectional area inside thehollow-fiber.S=(η_(w) *Q _(f) ·ΔP _(w0)′/η_(w0) *Q _(f0) *ΔP _(w)′)^(0.5)  Equation(6)where the respective parameters represent the following:

-   η_(w): viscosity of the liquid waste (Pa sec)-   η_(b0): viscosity of the liquid waste in the priming (Pa·sec)-   Q_(f): filtering flow rate (m/min)-   Q_(f0): filtering flow rate in the priming (ml/min)-   ΔP_(w)′: a difference of the pressure between blood side end and    liquid waste side end of the hollow-fiber membrane pore (mmHg)-   ΔP_(w0)′: a difference of the pressure between blood side end and    liquid waste side end of the hollow-fiber membrane pore in the    priming (mmHg)

Thus, calculated is a filter clogging factor [s(−)] which the reductionin ease of filtering of the filter is represented by a ratio of a crosssectional area inside the hollow-fiber using flow rate information,measured pressure indices and biometric information (viscosityinformation and so on). This makes it possible to eliminate theinfluences of errors included in the correction coefficient (k,k′) inthe calculation equation of the filter clogging factor and monitor thefilter clogging more precisely irrespective of factors affecting thepressure indices (filter structure, blood purification apparatus, bloodpurification circuit, flow rate, biometric factor).

In this embodiment, parameters r₀, A_(k), A_(m), τ and ΔX are defined bythe type of the filter and these parameters are collected as follows:

-   r₀, A_(k), A_(m), τ and ΔX: Manually input.-   Q_(f): Set by the blood purification apparatus and automatically    input continuously in real-time.

η_(w): Viscosity of liquid waste is measured several times a day using aviscometer and the inspection result is manually input.

ΔP_(w)′: Terms other than τΔΠ are measured by the blood purificationapparatus or pressure information collection apparatus and automaticallyinput continuously in real-time. For τΔΠ, the colloidal osmotic pressureof blood is measured by the colloidal osmotic pressure measurementseveral times a day and the inspection result is manually input or ablood albumin level Alb and blood globulin level Glob are measuredseveral times a day and a value obtained through an approximatecalculation using the following Equation (38) is manually input.ΔΠ=5.54Alb+1.43Glob  Equation (38)

-   ΔΠ: Colloidal osmotic pressure by protein (mmHg)-   Alb: Blood albumin level (g/dl)-   Glob: Blood globulin level (g/dl)-   σ: Staverman's coefficient of restitution (proportion of solute that    cannot permeate membrane) (−)    By the way, the input method is not limited to the above-described    methods.

As described above, calculating a clogging factor based on Equations (1)to (6) allows the clogging of a filter to be monitored more accuratelyirrespective of the presence/absence of factors affecting the pressureindices. Here, the influences of the filter on the pressure indices canbe removed by considering the filter structure information (diameter ofhollow-fiber, effective length of hollow-fiber, membrane area, membranethickness, rate of hollow area, rate of curved path, diameter ofmembrane pore, etc.). Furthermore, the influences of the flow rate onthe pressure indices can be removed by considering the flow rateinformation (blood flow rate, filtering flow rate, dialysis flow rate,etc.). Furthermore, the influences of biometric factors on the pressureindices are removed by integrating the measured pressure indices (Pa,Pv, Pf1, Pf2) and biometric information (viscosity (η_(b), η_(w)),etc.).

Furthermore, errors (a difference between filter structure informationof filter that is used actually and published standard values) includingfilter structure information or the influences of the blood purificationcircuit on the pressure measurements can be corrected by settingcoefficients (K, k) calculated from pressure indices during priming inthe clogging factor.

Furthermore, the influences of the kinds of the filter on the pressureindices or the influences of the blood purification circuits on thepressure measurements can be corrected by setting coefficients (K, k)calculated from pressure indices during priming in the clogging factor,and it is possible to calculate the clogging factor even if filterstructure information is not known.

Calculating this clogging factor makes it possible to express theclogging situation of the filter with a single factor when bloodpurification therapy is applied to patients in various clinicalconditions by calculating this clogging factor and using variousfilters, blood purification apparatuses and blood purification circuitswith various flow rate settings, and make comparisons.

The following effects can be expected to be achieved using this cloggingfactor, which would be impossible to be achieved using conventionalpressure indices:

1) Allows Safe Blood Purification Therapy Hardly Depending onExperiences

Use of this clogging factor allows even medical staff of littleexperience to simply grasp the clogging situation and also allowsmedical staff of rich experience to easily grasp the clogging situationwhen a new type of filter is used for the first time. Calculating theclogging factor in real time makes it possible to speedily take actions(increase in amount of coagulant, variation in blood flow rate)corresponding to the filter clogging.

2) Allows Collection or Exchange of Information Among Many Facilities

It is possible to evaluate the performance of and operation conditions afilter at various facilities with different blood purificationapparatuses and collects information on the development of the filterand setting of optimum operation conditions.

3) Provides a Basic Step Toward Automation

When it is an aim to automate the blood purification therapy using ablood purification apparatus, if the degree of clogging can be expressedusing a single index called a “clogging factor” that integrates allkinds of influencing factors, it will be possible to control theclogging more simply.

For a TMP, the above Equation (27) and the following Equations (39) to(48) can be used. Which equation should be used to calculate the TMP canbe determined according to the purpose as appropriate.TMP 1=(Pa+Pv)/2−(Pf 1+Pf 2)/2  Equation (39)

This Equation (39) (b in FIG. 4) expresses TMP in the center of thefilter.TMP 2=(Pa+Pv)/2−Pf 1  Equation (40)

This equation is a clinically defined equation of a hemofiltering,hemodiafiltering or plasmapheresis apparatus. Furthermore, this Equation(40) (c in FIG. 4) indicates a difference between the pressure on theblood side in the center of the filter and filtering pressure of theblood inflow portion.TMP 3=(Pa+Pv)/2−Pf 2  Equation (41)

This Equation (d in FIG. 4) is obtained by replacing the portion ofmeasuring Pf in Equation (40) by the blood outflow portion.TMP 5=(Pa+Pv)/2−Pf 1  Equation (42)

This Equation (e in FIG. 4) is a clinically defined equation of ahemofiltering, hemodiafiltering or plasmapheresis apparatus onegeneration ago and only represents a TMP of the blood inflow portion.TMP 2=(Pa+Pv)/2−Pf 1  Equation (43)

This Equation (f in FIG. 4) is a defined equation to define a blooddialyzing apparatus. This equation also represents a difference betweena pressure on the blood side of the blood outflow portion of the filterand a filtering pressure of the blood inflow portion.TMP 6=Pv−Pf 2  Equation (44)

This Equation (g in FIG. 4) only represents a TMP of the blood outflowportion.TMP 7=Pa−(Pf 1+Pf 2)/2 Equation (45)

This Equation (h in FIG. 4) expresses a difference between a pressure onthe blood side of the blood inflow portion of the filter and a filteringpressure at the center.TMP 8=Pv−(Pf 1+Pf 2)/2  Equation (46)This Equation (i in FIG. 4) represents a difference between a pressureon the blood side of the blood outflow portion of the filter and afiltering pressure at the center.

In order to accurately express a filtering pressure that contributes tothe passage of substances through membrane pores of the filter(effective filtering pressure), it is desirable to further calculate theabove-described TMP in combination with the colloidal osmotic pressureinformation of the blood. Especially, Equation (39) (b in FIG. 4),Equation (42) (e in FIG. 4) and Equation (44) (g in FIG. 4) can becombined with the colloidal osmotic pressure of blood to obtain Equation(27) (j in FIG. 4), Equation (47) (k in FIG. 4) and Equation (48) (l inFIG. 4), respectively and it is thereby possible to express thefiltering pressure that contributes to actual movement of substances(effective filtering pressure).TMP 9=(Pa+Pv)/2−(Pf 1+Pf 2)/2−σΔΠ  Equation (27)

-   ΔΠ: Colloidal osmotic pressure by protein (mmHg)-   σ: Staverman's coefficient of restitution (proportion of solute that    cannot permeate membrane (−))

This equation (j in FIG. 4) represents an effective filtering pressureat the center of the filter. The pressure that contributes to the actualpassage at the center of the filter (effective filtering pressure) iscalculated from this equation considering an osmotic pressure (ΔΠ) bythe membrane impermeable substances that exist on the blood side.TMP 10=Pa−Pf1−σΔΠ  Equation (47)

This equation (k in FIG. 4) represents an effective filtering pressureat the blood inflow portion of the filter. The pressure that contributesto the actual passage at the blood inflow portion (effective filteringpressure) is calculated from this equation considering an osmoticpressure (σΔΠ) by the membrane impermeable substances that exist on theblood side.TMP 11=Pv−Pf 2−σΔΠ  Equation (48)

This equation (1 in FIG. 4) represents an effective filtering pressureat the blood outflow portion of the filter. The pressure thatcontributes to the actual passage at the blood outflow portion(effective filtering pressure) is calculated from this equationconsidering an osmotic pressure (σΔΠ) by the membrane impermeablesubstances that exist on the blood side.

In Equation (27), an average between the value obtained from Equation(47) and the value obtained from Equation (48) is calculated. This valueis a typical TMP in the filter. Therefore, a clogging factor in lateraldirection is calculated by substituting this value into Equation (3),(4) or (6). By the way, the value is not limited to the average betweenthe value obtained from Equation (47) and the value obtained fromEquation (48), but it is also possible to use a TMP value obtained byother methods if it is at least a typical value of TMP of the filter.Thus, calculating the blood colloidal osmotic pressure information incombination makes it possible to grasp clogging in lateral direction ofthe filter precisely.

When a hemodialysis or hemodiafiltering is in progress, filtering(forward filtering) is performed from the blood side to the liquid waste(dialyzing fluid) side. In this case, back filtration whereby theeffective difference of the pressure is inverted near the blood outflowportion of the filter may take place (shaded area in FIG. 5). This backfiltration is more likely to occur in a filter with higher solutepermeability. With the recent increase in the use of a filter with highsolute permeability, which is advantageous in eliminating low molecularweight protein, back filtration is more likely to occur.

Once back filtration takes place, harmful substances such as endotoxincontained in a dialyzing fluid are mixed with the blood, provoking adanger of doing harm to the patient such as high fever. However, backfiltration can also be used to prevent clogging of membranes or promoteexchange of substances and new types of hemodiafiltering (push and pullhemodiafiltering, hemodiafiltering using a diaphragm dialyzer,semi-nephron hemodiafiltering, super flux hemodiafiltering, etc.), whichpositively take advantage of this back filtration, are also beingpracticed.

Adopting a TMP using the above Equations (27), (47) and (48) indicatingeffective filtering pressures makes it possible to precisely grasp andappropriately handle clogging in lateral direction including backfiltration.

As shown in this embodiment, by measuring at least two pressures (4pressures in this embodiment) selected from a group consisting of apressure in the blood inflow portion, pressure in the blood outflowportion, filtering pressure in the blood inflow portion and filteringpressure in the blood outflow portion, it is possible to grasp theabove-described back filtration noninvasively, continuously, inreal-time, precisely and specifically. This makes it possible to adjustthe amount of dosage of an anticoagulant appropriately and change thesetting of the flow rate of the blood.

Then, a bed-side system that implements the method according to thepresent invention will be explained. The bed-side system 6 shown in FIG.6 is composed in such a way that the flow rate of blood and amount ofdosage of medicine can be adjusted based on the information from acontinuous hematoclit monitor 64 and information from a filtermonitoring apparatus 61.

This bed-side system 6 is mainly constructed of the filter monitoringapparatus 61 that monitors clogging of a filter 621 for bloodpurification, the continuous hematoclit monitor 64 that stores, controlsand displays various kinds of information from a patient 63 and a bloodpurification apparatus 62 that performs blood purification processingbased on the information from the filter monitoring apparatus 61,adjusts the amount of medicine administered to the patient and adjuststhe flow rate of the blood.

As shown in FIG. 6, the filter monitoring apparatus 61 is mainlyconstructed of a pressure measurement section 612 that measures apressure at the filter 621, a calculation section 611 that calculates afilter clogging factor from the information from the continuoushematoclit monitor 64, pressure information from the pressuremeasurement section 612, flow rate information from the bloodpurification apparatus, filter structure information and otherinformation (viscosity information, protein concentration information,colloidal osmotic pressure information, filter structure information), amemory 613 that stores various kinds of information used for the filterclogging factor and calculation, and a display section 615 that displaysthe various kinds of information used for the filter clogging factor andcalculation.

As shown in FIG. 6, the blood purification apparatus 62 is mainlyconstructed of the filter 621, a blood inflow portion-side drip-chamber626 provided before the filter 621, a blood outflow portion-sidedrip-chamber 627 provided after the filter 621, a rotary pump 625provided on a blood circulation path 632 before the blood inflowportion-side drip-chamber 626, rotary pumps 630 and 629 that adjust theflow rate of liquid waste provided for tubes 628 and 631 mounted on acoupler of the filter 621, a flow rate control section 622 that controlsthe flow rate of the blood of the rotary pump 625 provided on the bloodcirculation path 632 based on the information on the filter monitoringapparatus 61, a medicine dosage section 624 that doses medicine such asan anticoagulant into the blood circulation path 632, and a medicinedosage amount control section 623 that controls the amount of medicinedosed into the blood circulation path 632 based on the information onthe filter monitoring apparatus 61.

The operation of the bed-side system in the above-describedconfiguration will be explained.

The blood circulates from the patient 63 along the blood circulationpath 632 and returns to the patient. 63 through the filter 621 mountedon the blood purification apparatus 62. At the blood purificationapparatus 62, a pressure Pa at the blood inflow portion-sidedrip-chamber 626, pressure Pv at the blood outflow portion-sidedrip-chamber 627, pressure Pf1 at the coupler on the blood inflowportion side of the filter 621, and pressure Pf2 at the coupler on theblood outflow portion side of the filter 621 are measured by thepressure measurement section 612 of the filter monitoring apparatus 61.Here, the pressure Pa at the blood inflow portion-side drip-chamber 626corresponds to the pressure in the filter blood inflow section, thepressure Pv at the blood outflow portion-side drip-chamber 627corresponds to the pressure of the filter blood outflow section, thepressure Pf1 at the coupler on the blood inflow portion side of thefilter 621 corresponds to the filtering pressure of the filter bloodinflow portion and the pressure Pf2 at the coupler on the blood outflowportion side of the filter 621 corresponds to the filtering pressure ofthe filter blood outflow portion.

These pressures are output from the pressure measurement section 612 tothe calculation section 611. The calculation section 611 calculates afilter clogging factor based on the pressure information from thepressure measurement section 612, patient information from thecontinuous hematoclit monitor 64, viscosity information from theoutside, protein concentration information, colloidal osmotic pressureinformation, filter structure information and flow rate information fromthe blood purification apparatus 62. The filter clogging factor invertical direction is calculated from the above-described Equation (1),(2) or (5) using at least two of blood viscosity information calculatedusing an Ht value from the continuous hematoclit monitor 64 and a TPvalue obtained from a clinical inspection, filter structure information,the pressure information from the pressure measurement section 612 andflow rate information obtained from the blood purification apparatus 62.The Ht value that determines a viscosity of blood can be collectedcontinuously using the continuous hematoclit monitor. On the other hand,the filter clogging factor in lateral direction is calculated from theabove-described Equation (3), (4) or (6) using at least two of theliquid waste viscosity information obtained from a clinical inspection,TMP calculated using the blood colloidal osmotic pressure informationobtained from the pressure measurement section 612 and a clinicalinspection, filter structure information and the flow rate informationobtained from the blood purification apparatus 62.

The filter clogging factor calculated from the calculation section 611is output to the control section 614. The control section 614 controlsthe flow rate control section 622 and the medicine dosage amount controlsection 623 of the blood purification apparatus 62. The flow ratecontrol section 622 controls the flow rate of the blood that circulatesinside the circulation path 632 based on the filter clogging factor. Forexample, the flow rate control section 622 sets an optimal blood flowrate based on a table that associates a filter clogging factor with ablood flow rate and outputs the flow rate information to the rotary pump625. The rotary pump 625 adjusts the flow rate of the blood based on theflow rate information from the flow rate control section 622.

Furthermore, the flow rate control section 622 controls the flow rate ofliquid waste that passes through the tubes 628 and 631 of the filter 621based on the filter clogging factor. For example, the flow rate controlsection 622 sets an optimal liquid waste flow rate based on a table thatassociates a filter clogging factor with a liquid waste flow rate andoutputs the flow rate information to the rotary pumps 630 and 629.

The rotary pumps 630 and 629 adjust the flow rate of liquid waste basedon the flow rate information from the flow rate control section 622. Atthis time, the flow rate control section 622 can control the rotarypumps 630 and 629 equally or control them individually according to theclogging situation of the filter 621 (can be determined using TMPs 9 to11).

The medicine dosage amount control section 623 controls the amount ofmedicine to be dosed into the circulation path 632 based on the filterclogging factor. For example, the medicine dosage amount control section623 sets an optimal amount of medicine dosage based on a table thatassociates filter clogging information with an amount of medicine dosageand outputs the medicine dosage amount information to the medicinedosage section 624. The medicine dosage section 624 adjusts the amountof medicine dosage based on the medicine dosage amount information fromthe medicine dosage amount control section 623 and doses the adjustedamount of medicine dosage into the circulation path 632.

More specifically, when the filter clogging factor in vertical directionF increases and/or the filter clogging factor in vertical direction Sdecreases, the medicine dosage amount control section 623 makes asetting so as to increase the amount of dosage of an anticoagulant andcontrols the medicine dosage section 624 so that this amount of theanticoagulant is dosed into the circulation path 632. Furthermore, theflow rate control section 622 makes a setting so as to increase theblood flow rate and controls the rotary pump 625 so that the blood iscirculated at this flow rate. This can prevent the progress of filterclogging and extend the time until the filter is clogged. Furthermore,this can also prevent the blood inside the filter, when the blood in thecircuit is completely returned to the patient to terminate bloodpurification, from remaining (residual blood) or prevent blood lossbecause of the inability to return the blood in the circuit to thepatient due to drastic clogging (inability to recover blood).

When the filter clogging factor f in lateral direction increases and/orthe filter clogging factor s in lateral direction decreases, themedicine dosage amount control section 623 makes a setting so as toincrease the amount of dosage of an anticoagulant and controls themedicine dosage section 624 so that this amount of the anticoagulant isdosed into the circulation path 632. Furthermore, the flow rate controlsection 622 makes a setting so as to decrease the flow rate of blood andcontrols the rotary pumps 630 and 629 so that the liquid waste isfiltered at this flow rate. This can reduce the filtering performanceper unit time and extend the time until the filter is clogged. Here, acase where control is performed to reduce the flow rate of liquid wasteis explained, but it is also possible to perform control to increase theflow rate of liquid waste according to the situation.

Thus, the bed-side system according to this embodiment can performcalculation of the filter clogging factors and monitoring of filterclogging, etc., according to this embodiment at the bed side inreal-time. This bed-side system can also store information collected oranalyzed at the bed side and use the information to adjust the flow rateof blood or liquid waste or the amount of medicine dosage, etc.

The configurations of the bed-side system and the filter monitoringapparatus are not limited to the configurations shown in FIG. 6. Thatis, it is possible to calculate the filter clogging factor from theabove Equations (1) to (6) and change the configuration of the apparatusbased on the information in various ways within a range in which bloodpurification is controllable.

Then, practical examples that have been conducted to verify the effectsof the present invention will be explained. FIG. 7 illustrates avariation of the clogging factor (F) in the vertical direction whensustained blood filtering was performed. Here, a blood purificationapparatus KM-8600P (product name, manufactured by Kuraray Medical Co.,Ltd.), blood purification circuit KPD-8610 (product name, manufacturedby Kuraray Medical Co., Ltd.) and hemofilter APF-06S (product name,manufactured by Asahi Medical Co., Ltd.) were used. F (%) was calculatedaccording to Equation (2) when sustained blood filtering was performed.

As is apparent from FIG. 7, the clogging in the vertical direction thatprogress gradually starts to accelerate drastically around 19:00. Thus,monitoring the variation of the clogging factor (F) makes it possible tokeep track of the progress of the clogging in the vertical direction.

FIG. 8 illustrates a variation of the clogging factor (f) in thehorizontal direction when sustained blood filtering was performed. Here,a blood purification apparatus KM-8600P (product name, manufactured byKuraray Medical Co., Ltd.), blood purification circuit KPD-8610 (productname, manufactured by Kuraray Medical Co., Ltd.) and hemofilter APF-06S(product name, manufactured by Asahi Medical Co., Ltd.) were used f (%)was calculated according to Equation (4) when sustained blood filteringwas performed.

As is apparent from FIG. 8, because the clogging factor f increased,dosage of an anticoagulant (nafamostat mesylate) was increasedtemporarily from 20 mg/hr to 25 mg/hr at the point (1) in the figure andas a result, the increase of f was suppressed. Then, an increase of fwas observed again and so dosage of the anticoagulant (nafamostatmesylate) was increased from 20 mg/hr to 25 mg/hr at the point (2) and anew anticoagulant (low molecular weight heparin) was dosed at a rate of100 U/hr at the point (3). This caused the clogging factor f to show adeclination. However, since the amount of urine started to decrease withthe deterioration of the condition of the whole body, the flow rate offiltering was increased at the point (4) to increase the amount ofharmful substances removed from the body, and as a result drasticprogress of clogging in the horizontal direction of the filter (drasticincrease of f) was observed.

Monitoring the clogging factor in the horizontal direction in this waymakes it possible to adjust dosage of the anticoagulant appropriately.

FIG. 9 illustrates a variation of a pressure index Pa−Pv and a variationof the clogging factor (F) in the vertical direction caused by avariation in the blood flow rate. Here, a blood purification apparatusKM-8600P (product name, manufactured by Kuraray Medical Co., Ltd.),blood purification circuit KPD-8610 (product name, manufactured byKuraray Medical Co., Ltd.) and hemofilter APF-06S (product name,manufactured by Asahi Medical Co., Ltd.) were used. FIG. 9 shows thepressure index Pa−Pv in a stabilization period (A) with a blood flowrate of 100 m/min and filtering flow rate of 15 ml/min after sustainedblood filtering is started and the clogging factor F (%) in the verticaldirection calculated using Equation (2), and the pressure index Pa−Pvimmediately after only the blood flow rate is reduced to 80 m/min (B)and the clogging factor F (%) in the vertical direction calculated usingEquation (2).

The degrees of filter clogging immediately after the blood flow rate ischanged (B) and immediately before the blood flow rate is changed (A)are considered to be the same. As is apparent from FIG. 9, even if theblood flow rate is reduced, the clogging factor F does not change butthe pressure index Pa−Pv decreases. Thus, when the flow rate changes, itis difficult to monitor the filter clogging accurately with the pressureindex alone and it is appreciated that the clogging factor of thepresent invention is appropriate as the parameter to monitor theclogging condition.

FIG. 10 shows a simulation curve indicating a relationship between thepressure index Pa−Pv and clogging factor F (%) in the vertical directioncalculated from Equation (2) when sustained blood filtering was appliedto a patient with a blood flow rate of 100 ml/min, filtering flow rateof 15 ml/min and total serum protein concentration of 7.0 g/dl. A bloodpurification apparatus ACH-10 (product name, manufactured by AsahiMedical Co., Ltd.), blood purification circuit CHF-400N (product name,manufactured by Asahi Medical Co., Ltd.) and hemofilter APF-06S (productname, manufactured by Asahi Medical Co., Ltd.) were used. As is apparentfrom FIG. 10, when the pressure index Pa−Pv is 50 mmHg, F is 31.1% whena hematocrit value is 20%, while F is 13.4% when the hematocrit value is40%.

Thus, it is appreciated that even if only the pressure index Pa−Pv ismonitored, when biometric information (factors affecting bloodviscosity) changes, it is not possible to evaluate the filter cloggingaccurately. From FIG. 9 and FIG. 10, it is appreciated that the pressureindex Pa−Pv is not sufficient as the parameter for monitoring the filterclogging factor.

FIG. 11 illustrates a variation of the clogging factor (s) in thehorizontal direction when sustained blood filtering was performed. Here,a blood purification apparatus KM-8600P (product name, manufactured byKuraray Medical Co., Ltd.), blood purification circuit KPD-8610 (productname, manufactured by Kuraray Medical Co., Ltd.) and hemofilter APF-06S(product name, manufactured by Asahi Medical Co., Ltd.) were used.

FIG. 11 shows a variation of the clogging factor s (%) in the horizontaldirection calculated using Equation (6) when sustained blood filteringwas performed. At the point (5) in the figure, a 10 mg anticoagulant(nafamostat mesylate) was dosed into the blood purification circuit inone shot and the sustained dosage was increased from 20 mg/hr to 25mg/hr, and as a result the s value was suppressed approximately 4 hourslater.

Thus, monitoring the clogging factor in the horizontal direction makesit possible to adjust dosage of the anticoagulant, etc., appropriately.

From the above-described practical examples, it is appreciated that theclogging factors F, f and s of the present invention are appropriate asparameters to monitor the clogging situation of the filter.

Thus, the method according to this embodiment can discover clogging of afilter in an early stage, adjust dosage of the anticoagulantappropriately without overdosage and change the setting of the flow rateof blood to prevent the progress of clogging of the filter. Furthermore,it is also possible to predict the time during which blood purificationcan be executed (completion timing), which allows medical staff toprepare for terminating blood purification with a sufficient time.Furthermore, it can also prevent blood loss caused by the bloodremaining in the filter (residual blood) at the end of bloodpurification. It also reduces the danger of blood cells being suctionedby a strong negative pressure, causing destruction of blood cells(hemolysis, etc.). It further allows more effective operating conditionsto be set considering the reduction in substance removing ability(clearance) due to filter clogging.

By controlling back filtration, it is also possible to set the flow rateconsidering back filtration of each filter.

Thus, by preventing filter clogging and controlling back filtration, itis possible to perform blood purification more safely and economically.

Furthermore, it is also possible to evaluate how clogging occurs in eachfilter and how back filtration occurs, and use these evaluation resultsfor the development of a filter in which clogging hardly occurs or thedevelopment of a filter with controlled back filtration.

The present invention is not limited to the above-described embodiments,but can be implemented modified in various ways. For example, thenumerical values and materials in the above-described embodiments arepresented for illustrative purposes and not limitative, and can beimplemented modified in various ways.

The present invention is applicable to an evaluation of clogging fortubular-like structures, for example water purification apparatus,transport tube for a liquid medicine, a water pipe, ink pipe, inknozzle, or spraying tube for a liquid medicine.

As explained above, the present invention measures at least twopressures selected from the group consisting of a pressure in the bloodinflow portion, a pressure in the blood outflow portion, a filteringpressure in the blood inflow portion, and a filtering pressure in theblood outflow portion and calculates a filter clogging factor invertical direction and lateral direction by using at least two of themeasured pressures, flow rate information (conditions during operation),biometric information (viscosity information), a correction coefficientcalculated from pressure indices in the priming, structure information.Thereby, it is possible to discover filter clogging in verticaldirection and/or lateral direction in an early stage, appropriatelyadjust dosage of an anticoagulant without overdosage, change a bloodflow rate setting and prevent the progress of filter clogging.

This application is based on the Japanese Patent Application No.2002-187949 filed on Jun. 27, 2002, entire content of which is expresslyincorporated by reference herein.

1. Method for calculating a clogging factor of a filter composed ofhollow-fiber membrane, which has a blood inflow portion and a bloodoutflow portion, for filtering a blood by passing said blood, saidmethod comprising the steps of: measuring at least two pressure selectedfrom the group consisting of a pressure in said blood inflow portion, apressure in said blood outflow portion, a filtering pressure in saidblood inflow portion, and a filtering pressure in said blood outflowportion; and calculating a filter clogging factor indicating thereduction in flowing ease of the blood in said filter and/or a filterclogging factor indicating the reduction in ease of filtering of saidfilter, by using the measured pressure.
 2. Method for calculating aclogging factor of a filter according to claim 1, wherein a filterclogging factor indicating the reduction in flowing ease of the blood insaid filter is calculated by using a viscosity of blood.
 3. Method forcalculating a clogging factor of a filter according to claim 1, whereina filter clogging factor indicating the reduction in ease of filteringof said filter is calculated by using a viscosity of liquid waste. 4.Method for calculating a clogging factor of a filter according to claim1, wherein a filter clogging factor indicating the reduction in flowingease of the blood in said filter is calculated by using structureinformation and/or flow rate information of said filter.
 5. Method forcalculating a clogging factor of a filter according to claim 1, whereina filter clogging factor indicating the reduction in ease of filteringof said filter is calculated by using structure information and/or flowrate information of said filter.
 6. Method for calculating a cloggingfactor of a filter according to claim 2, wherein a filter cloggingfactor [F(%)], which the reduction in flowing ease of the blood in saidfilter is represented by the decreasing rate in a cross sectional areainside said hollow-fiber, is calculated by using the Equation (1):F=100{1−[10−9·K·l·η _(b)·(Q _(b) −Q _(f)/2)/N/ΔP_(b)′/π]^(0.5) /R ₀²}  Equation (1) where K represents a correction coefficient (−), 1 brepresents viscosity (Pa·sec) of the blood, Q_(b) represents flow rate(ml/min) of the blood flowing into the filter, Q_(f) representsfiltering flow rate (ml/min), N represents the number of hollow-fibers(−), ΔP_(b)′ represents a difference (mmHg) of the pressure between bothends of the hollow-fiber, I represents an effective length (m) of thehollow-fiber, and R₀ represents the radius (m) inside the hollow-fiberthat the clogging does not occur.
 7. Method for calculating a cloggingfactor of a filter according to claim 2, wherein a filter cloggingfactor [F(%)] which the reduction in flowing ease of the blood in saidfilter is represented by the decreasing rate in a cross sectional areainside said hollow-fiber is calculated by using the Equation (2):F=100{1−[K′·η_(b)·(Q _(b) −Q _(f)/2)/ΔP_(b)′]0.5}  Equation (2) where K′represents a correction coefficient (−), η_(b) represents viscosity(Pa·sec) of the blood, Q_(b) represents flow rate (ml/min) of the bloodflowing into the filter, Q_(f) represents filtering flow rate (ml/min),and ΔP_(b)′ represents a difference (mmHg) of the pressure between bothends of the hollow-fiber.
 8. Method for calculating a clogging factor ofa filter according to claim 1, a filter clogging factor indicating thereduction in flowing ease of the blood in said filter is calculated inreal-time.
 9. Method for calculating a clogging factor of a filteraccording to claim 3, wherein a filter clogging factor [f(%)], which thereduction in ease of filtering of said filter is represented by thedecreasing rate in a cross sectional area of pore of said hollow-fiber,is calculated by using the Equation (3):f=100[1−(10⁻⁹ ·k·τ·ΔX·η _(w) ·Q _(f) /r ₀ /A _(k) /A _(m) /ΔP _(w) ′)^(0.5)]  Equation (3) where k represents a correction coefficient (−),τrepresents a rate of curved path, ΔX represents a thickness of amembrane, 11 w represents a viscosity of liquid waste passing a filter(Pa·sec), Q_(f) represents filtering rate (ml/min), r₀ represents theradius (m) of a hollow-fiber membrane pore that the clogging does notoccur, ΔP_(w)′ represents a difference of the pressure between the bloodside end and the liquid waste side end in the membrane pore of thefilter (mmHg), A_(k) represents a proportion of a cross sectional areaof the membrane pore to a unit area of the membrane in the filter, andA_(m) represents an area (m) of the membrane in the filter.
 10. Methodfor calculating a clogging factor of a filter according to claim 3,wherein a filter clogging factor [f(%)], which the reduction in ease offiltering of said filter is represented by the decreasing rate in across sectional area of pore of said hollow-fiber, is calculated byusing the Equation (4):f=100[1−(k′·η_(w)·Q_(f)/ΔP_(w)′)^(0.5)]  Equation (4) where k′represents a correction coefficient (−), η_(w) represents a viscosity ofliquid waste passing a filter (Pa·sec), Q_(f) represents filtering rate(ml/min), r represents the radius (m) of a hollow-fiber membrane porethat the clogging does not occur, and ΔP_(w)′ represents a difference ofthe pressure between the blood side end and the liquid waste side end inthe membrane pore of the filter (mmHg).
 11. Method for calculating aclogging factor of a filter according to claim 1, wherein, a filterclogging factor indicating the reduction in ease of filtering of saidfilter is calculated in real-time.
 12. Method for calculating a cloggingfactor of a filter according to claim 1, wherein a filter cloggingfactor [S(−)] which the reduction in flowing ease of the blood in saidfilter is represented by the decreasing rate in a cross sectional areainside said hollow-fiber is calculated by using the Equation (5):S=[η_(b)·(Q _(b)-Q_(f)/2)·ΔP_(b0)′/η_(b0)/(Q_(b0) −Q_(f0)/2)/ΔP_(b)]^(0.5)  Equation (5) wherein η_(b) represents viscosity(Pa·sec) of the blood flowing in the hollow-fiber, η_(b0) representsviscosity (Pa·sec) of the priming liquid in the priming, Q_(b)represents flow rate (ml/min) of the blood flowing into the filter,Q_(b0) represents flow rate (ml/min) of the priming liquid flowing intothe filter in the priming, Q_(f) represents filtering flow rate (mmin),Q_(f0) represents filtering flow rate (mmin) in the priming, ΔP_(b)′represents a difference (mmHg) (Pa−Pv) of the pressure between both endsof the hollow-fiber, and ΔP_(b0)′ represents a difference (mmHg) of thepressure between both ends of the hollow-fiber in the priming. 13.Method for calculating a clogging factor of a filter according to claim1, wherein a filter clogging factor [s(−)] which the reduction in easeof filtering of said filter is represented by the decreasing rate in across sectional area of membrane pore of said hollow-fiber is calculatedby using the Equation (6):s=(η _(w) ·Q _(f) ·ΔP _(w0)′/η_(w0) /Q _(f0) /ΔP _(w)′)^(0.5)  Equation(6) wherein η_(w), represents viscosity (Pa·sec) of the liquid waste,η_(b0) represents viscosity (Pa·sec) of the liquid waste in the priming,Q_(f) represents filtering flow rate (mmin), Q_(f0) represents filteringflow rate (ml/min) in the priming, ΔP_(w)′ represents a difference(mmhg) of the pressure between blood side end and liquid waste side endof the hollow-fiber membrane pore, Δ_(Pw) 0′ represents a difference(mmHg) of the pressure between blood side end and liquid waste side endof the hollow-fiber membrane pore in the priming, and s represents aratio of cross sectional areas in the hollow-fiber membrane pore of thefilter.
 14. Method for calculating a clogging factor of a filteraccording to claim 1, wherein, an average of ΔP_(w)′ in said bloodinflow portion and ΔP_(w)′ in said blood outflow portion is used asΔP_(w)′.
 15. Method for monitoring a clogging of a filter comprising thesteps of: calculating a clogging factor of a filter by using a methodfor calculating a clogging factor of a filter according to any one ofclaim 1; and monitoring a clogging of a filter on the basis of theclogging factor of a filter.
 16. Apparatus of monitoring a clogging of afilter comprising: means for calculating a clogging factor of a filterby using a method for calculating a clogging factor of a filteraccording to any one of claim 1; and means for monitoring a clogging ofa filter on the basis of the clogging factor of a filter.
 17. Bed-sidesystem comprising apparatus of monitoring a clogging of a filteraccording to claim 16.